Relación entre la hipertrabeculación ventricular izquierda y el ejercicio.

(1)

Dra. Inés García Lunar.

CNIC / H. Quirónsalud Madrid 14/Diciembre/2019

Relación entre la hipertrabeculación

ventricular izquierda y el ejercicio.

(2)

Introducción: Miocardiopatía no compactada. Definición.

• La miocardiopatía no compactada (MNC) es una anormalidad estructural del miocardio de etiología y mecanismo inciertos (componente genético).

726 Circulation Research September 15, 2017

of DCM has been difficult to standardize given the influence of body size, athletic training, and biological heterogeneity on measurements of left ventricular volume and contractile func- tion. Prevalence data also vary when disease expression is re- lated to age (HCM),

^23,24

age and sex (Brugada syndrome),

^25–27

or is present at birth (LQT).

^28,29

In addition, founder effects may influence prevalence and perceptions of disease severity (ARVC).

^30,31

Table 1 presents a summary of disease prevalence in chil- dren and adults for HCM, DCM, ARVC, RCM, and chan- nelopathies. A disease prevalence of 1:250 to 500 for HCM in adults seems to be similar in all races, and disease expres- sion usually occurs in adolescents and young adults, whereas

Figure 7. Restrictive cardiomyopathy.

A, Cardiac specimen sectioned to reveal a 4-chamber view: the small nonhypertrophied ventricles look like appendages of the very dilated atria. Note the absence of pericardial, endocardial, or valvular disease. B, The restriction is primarily of the myocardium, which reveals myocyte disarray. Azan stain.

Figure 8. Endocardial fibroelastosis. A, Cross section of the ventricles: note the whitish, thickened, pearly colored

endocardium. B, At histology, the endocardial thickness consists of elastic fibers. Weigert stain.

Figure 9. Left ventricular noncompaction. A, Specimen cut to reveal 4-chamber view with coarse trabeculations in the left ventricular cavity and deep intertrabecular spaces. B, Histology:

the intertrabecular subendocardial spaces mostly reach the epicardium. Azan stain.

Downloaded from http://ahajournals.org by on December 9, 2019

Porción endocárdica (no compactada) de aspecto espongiforme (trabéculas prominentes y recesos intertrabeculares) que se comunican con la cavidad de VI y están rellenos de sangre.

Porción epicárdica (compactada)

Towbin. Circ Res 2017

• Afectación predominante: VI.

• Se caracteriza por el siguiente patrón:

726 Circulation Research September 15, 2017

of DCM has been difficult to standardize given the influence of body size, athletic training, and biological heterogeneity on measurements of left ventricular volume and contractile func- tion. Prevalence data also vary when disease expression is re- lated to age (HCM),

^23,24

age and sex (Brugada syndrome),

^25–27

or is present at birth (LQT).

^28,29

In addition, founder effects may influence prevalence and perceptions of disease severity (ARVC).

^30,31

Table 1 presents a summary of disease prevalence in chil- dren and adults for HCM, DCM, ARVC, RCM, and chan- nelopathies. A disease prevalence of 1:250 to 500 for HCM in adults seems to be similar in all races, and disease expres- sion usually occurs in adolescents and young adults, whereas

Figure 7. Restrictive cardiomyopathy.

A, Cardiac specimen sectioned to reveal a 4-chamber view: the small nonhypertrophied ventricles look like appendages of the very dilated atria. Note the absence of pericardial, endocardial, or valvular disease. B, The restriction is primarily of the myocardium, which reveals myocyte disarray. Azan stain.

Figure 8. Endocardial fibroelastosis. A, Cross section of the ventricles: note the whitish, thickened, pearly colored

endocardium. B, At histology, the endocardial thickness consists of elastic fibers. Weigert stain.

Figure 9. Left ventricular noncompaction. A, Specimen cut to reveal 4-chamber view with coarse trabeculations in the left ventricular cavity and deep intertrabecular spaces. B, Histology:

the intertrabecular subendocardial spaces mostly reach the epicardium. Azan stain.

(3)

• Clasificación: Miocardiopatía primaria (genética) por la AHA (2006) y miocardiopatía no clasificada por la ESC (2008).

Maron. Circulation 2006.

McKenna et al Classification of Cardiomyopathies 727

it is uncommon in children.^23,24 Robust data on the epidemi- ology of DCM are lacking, but estimates suggest incidence and prevalence figures of approximately twice those seen in HCM.³² Incidence in children is greatest in the first year of life (4.58/100 000) and much less common from age 1 to 18 years (0.34/100 000).²⁰ The prevalence of ARVC has not been systematically studied, but is estimated at 1/2000 to 5000^33,34; robust epidemiological data are lacking in part because of the multiple clinical evaluations required for diagnosis. ARVC in childhood is rare, and, like in HCM, disease expression usually occurs during adolescence and early adulthood, but may

develop at any age, in keeping with the concept of genetically determined cardiomyopathy.³⁴

For LQT syndrome, a prevalence of 1:2000 has been established in neonates, and data suggest that this is similar for all ages and races, although event rates differ for LQT1, LQT2, and LQT3 with respect to age and sex.^28,29,35

Criteria for the diagnosis of Brugada syndrome include a type 1 ECG pattern (coved ST-segment elevation with J point amplitude ≥0.2 mV followed by negative T wave) with at least 1 additional feature suggestive of arrhythmia (eg, unexplained sudden cardiac death aged <45 years in a relative).^25,36 Figure 10. American Heart Association Classification of Cardiomyopathies. Primary cardiomyopathies in which the clinically relevant disease processes solely or predominantly involve the myocardium. The conditions have been segregated according to their genetic or nongenetic causes. *Predominantly nongenetic; familial disease with a genetic origin has been reported in a minority of cases. ARVC/D indicates arrhythmogenic right ventricular cardiomyopathy/dysplasia; CPVT, catecholaminergic polymorphic ventricular tachycardia;

DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LQTS, long-QT syndrome; LVNC, left ventricular noncompaction;

Figure 11. European Society of Cardiology Classification of Cardiomyopathies. Summary of proposed classification system.

ARVC indicates arrhythmogenic right ventricular cardiomyopathy; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; and RCM, restrictive cardiomyopathy. From Elliott et al¹⁸ with permission of the publisher. Copyright

McKenna et al Classification of Cardiomyopathies 727

it is uncommon in children.^23,24 Robust data on the epidemi- ology of DCM are lacking, but estimates suggest incidence and prevalence figures of approximately twice those seen in HCM.³² Incidence in children is greatest in the first year of life (4.58/100 000) and much less common from age 1 to 18 years (0.34/100 000).²⁰ The prevalence of ARVC has not been systematically studied, but is estimated at 1/2000 to 5000^33,34; robust epidemiological data are lacking in part because of the multiple clinical evaluations required for diagnosis. ARVC in childhood is rare, and, like in HCM, disease expression usually occurs during adolescence and early adulthood, but may

develop at any age, in keeping with the concept of genetically determined cardiomyopathy.³⁴

For LQT syndrome, a prevalence of 1:2000 has been established in neonates, and data suggest that this is similar for all ages and races, although event rates differ for LQT1, LQT2, and LQT3 with respect to age and sex.^28,29,35

Criteria for the diagnosis of Brugada syndrome include a type 1 ECG pattern (coved ST-segment elevation with J point amplitude ≥0.2 mV followed by negative T wave) with at least 1 additional feature suggestive of arrhythmia (eg, unexplained sudden cardiac death aged <45 years in a relative).^25,36

Figure 10. American Heart Association Classification of Cardiomyopathies. Primary cardiomyopathies in which the clinically relevant disease processes solely or predominantly involve the myocardium. The conditions have been segregated according to their genetic or nongenetic causes. *Predominantly nongenetic; familial disease with a genetic origin has been reported in a minority of cases. ARVC/D indicates arrhythmogenic right ventricular cardiomyopathy/dysplasia; CPVT, catecholaminergic polymorphic ventricular tachycardia;

DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LQTS, long-QT syndrome; LVNC, left ventricular noncompaction;

Figure 11. European Society of Cardiology Classification of Cardiomyopathies. Summary of proposed classification system.

ARVC indicates arrhythmogenic right ventricular cardiomyopathy; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; and RCM, restrictive cardiomyopathy. From Elliott et al¹⁸ with permission of the publisher. Copyright

Elliot. EHJ 2008.

Introducción: Miocardiopatía no compactada. Clasificación.

(4)

Introducción: Miocardiopatía no compactada.

Etiopatogenia.

detected by retrospective clonal analysis, are present before activation of Mesp1 or Smarcd3, thus before gastrulation^22,26,29.

Live imaging of early heart formation. Live- imaging experiments of mouse embryos at the time of heart tube formation have provided insight into the dynam- ics of myocardial differentiation¹⁹. Myocardial differentiation was shown to occur in two phases. The first wave occurs at the early head- fold stage during 5–6 h and corresponds to the formation of the cardiac crescent. A pause of 5–7 h is observed before myocardial differentiation is re- initiated when the heart tube starts looping, providing cells for the elongation of the heart

tube. These waves of differentiation are consistent with the two myocardial lineages ingressing sequentially through the primitive streak and thus reaching the heart region sequentially.

Myocardial sublineages. Further information about myocardial sublineages ^(FIG. 2) came from analysis of clonal contributions to the anterior skeletal muscles of the head and neck, which also express Actc1 during development. These anterior muscles, which derive from mesoderm present in the pharyngeal arches³¹^(BOX 1), are clearly detectable by E14.5. Retrospective clonal analysis at E14.5 showed that masticatory muscles, derived from the mesoderm of the first pharyngeal arch, share

NATURE REVIEWS | CARDIOLOGY VOLUME 15 | NOVEMBER 2018 | 707

C A R D I A C D E V E L O P M E N T

Cardiogenic mesoderm E7.25

Fetal heart ventricular wall

E13.5

Fetal heart E16.5 Cardiac crescent

E7.5 Looped heart tube

E8.5 Chamber formation

E10.5

Looped heart tube Cardiac progenitors Endoderm

LV RA OFT

LA

RV

Primitive streak

Pharyngeal arches

Proepicardium Cardiac

crescent

Pericardium Ap

Vp

Coronary artery Coronary vein

Smooth muscle

ICV

Epicardium PV

Coronary vessels Pericardium

Endocardium Myocardium

Epicardium Endocardium Myocardium

Valves

Trabeculations Conduction system Interstitial ﬁbroblasts

Interstitial ﬁbroblasts

IVS

LA

RV LV Ao SCV

RA PA

Fig. 1 | Cardiogenesis stages in the mouse. After gastrulation, cardiac progenitors migrate laterally towards the head folds at embryonic day (E) 7.25 (arrow), where the cardiac crescent forms (E7.5). At E8.5, the heart tube, which is composed of an inner layer of endocardium (yellow) and an outer layer of myocardium (orange), elongates from both the arterial (Ap) and venous (Vp) poles (arrows). At E10.5, cardiac chambers are visible as bulges from the heart tube.

The proepicardium (E8.5) gives rise to the epicardium, which covers the myocardial surface and gives rise to interstitial fibroblasts (arrows), shown in the ventricular wall (E13.5). Coronary veins form superficially compared with coronary arteries. The different compartments and tissues of the heart are shown at E16.5. Ao, aorta; ICV, inferior caval vein;

IVS, interventricular septum; L A , left atrium; LV, left ventricle; OFT, outflow tract; PA , pulmonary artery ; PV, pulmonary vein; RA , right atrium; RV, right ventricle; SCV, superior caval vein. Adapted with permission from REF.¹⁹², Cold Spring Harbor Laboratory Press.

Meilhac. Nat reviews 2018.

(5)

• Se han identificado varias mutaciones (genes sarcoméricos, citoesqueleto y membrana nuclear) relacionadas con la enfermedad y existe una asociación familiar .

• ↓ prevalencia global : 0,01-0,3% de los adultos referidos para ecocardiograma; hasta 3-4% en pacientes con diagnóstico de IC.

• Varias formas clínicas:

- Benigna (función sistólica y diastólica preservada, aprox. 35% casos).

- MNC arritmogénica.

- MNC hipertrófica/dilatada/mixta.

- MNC restrictiva.

- MNC biventricular o con afectación de VD.

- MNC asociada a otras C. congénitas.

• ↑ riesgo tromboembolismo.

Introducción: Miocardiopatía no compactada.

Características.

Towbin. Lancet 2015.

(6)

• Diagnóstico: Técnicas de imagen.

• Problema: Solapamiento fenotípico con otras entidades (MCH, MCD, algunas condiciones fisiológicas).

Introducción: Miocardiopatía no compactada. Diagnóstico.

- Ratio NC/C ≥ 2 en telesístole (eje corto).

- Capa epicárdica fina compactada y capa endocárdica no compactada con trabéculas y recesos profundos.

- Paso de flujo por Doppler color entre las trabéculas.

- Localización predominante: apical, lateral e inferior.

- Ausencia de otras alteraciones cardíacas. Jenni. Heart 2001.

ECOCARDIOGRAFÍA

476 Circulation August 5, 2014

low prevalence of the other primary cardiomyopathies in the general population, it is unlikely that all such individuals suf- fer from LVNC. Indeed, the most probable explanation for the increased trabeculations and recesses observed in these states is a physiologically determined epiphenomenon in response to a chronic increase in cardiac preload.

Pregnancy is associated with doubling of maternal cardiac preload for at least 4 months.

¹⁰

Based on the cardiovascular changes observed in pregnancy, a longitudinal pregnancy model was applied to evaluate whether increased LV trabecu- lations observed in the aforementioned situations are a cardiac response to increased preload rather than LVNC. We hypoth- esized that women with a morphologically normal LV myo- cardium may develop LV trabeculations during pregnancy and that such changes would resolve within a few weeks of deliv- ery, after normalization of blood volume.

Methods

Subjects

We conducted a prospective longitudinal echocardiographic study of 102 primigravida pregnant women (66 white, 36 black) between 2010 and 2013. The women were recruited from 2 specialized ante- natal units in south London (University Hospital Lewisham and St. George’s Hospital NHS Trust). All women provided consent and were evaluated by a self-reported health questionnaire, which required information relating to the presence of cardiac symptoms, drug history, previous miscarriages, and family history of premature cardiovascular disease or sudden cardiac death; physical examina- tion; urine dipstick; 12-lead ECG; and 2-dimensional echocardiogra- phy. The women’s ethnicity was self-assigned. All women underwent

repeat 12-lead ECG and 2-dimensional echocardiography between 28 to 36 weeks of gestation and 3 to 12 months postpartum.

Selection criteria for the study included age from 18 to 35 years, primigravida status, singleton pregnancy, black or white ethnicity, absence of cardiac symptoms, a structurally normal heart on echo- cardiography without any evidence of increased LV trabeculations, and the ability to perform a full range of high-quality images with clear definition of the endocardium in the standard planes in the third trimester of pregnancy.

12-Lead ECG

A standard 12-lead ECG was performed with a Philips Pagewriter Trim III (Bothel, WA) and analyzed as previously described.

^11,12

Echocardiography

Two-dimensional echocardiography was performed by a cardiologist with accreditation in echocardiography (S.G.) with either the Philips Sonos 7500 or Philips iE33. Standard cardiac views were obtained and analyzed according to protocols specified by the American Society of Echocardiography.

¹³

All measurements were recorded as absolute values. Cardiac dimensions and volumes were assessed as previously described.

⁸

LV mass was calculated with the formula of Devereux and indexed for body surface area.

¹⁴

Assessment of dia- stolic function included pulsed-wave Doppler across the mitral valve and tissue Doppler velocity imaging of the septal and lateral mitral valve annuli in the apical 4-chamber view. Stroke volume was cal- culated as the product of aortic Doppler flow velocity time integral and cross-sectional area of the LV outflow tract.

¹⁵

Cardiac output was calculated as the product of stroke volume and heart rate derived from ECG monitoring.

¹⁵

Mean arterial blood pressure was calculated as diastolic blood pressure minus systolic blood pressure divided by diastolic blood pressure. Total vascular resistance was calculated (in dynes·s·cm

⁻⁵

) with the standard formula: Total vascular resistance Figure 1. Graphic representation of increased left ventricular (LV) trabeculations and intertrabecular recesses on short-axis

echocardiographic views and interpretation criteria of the Chin et al

²

and Jenni et al

³

for LV noncompaction (LVNC). X indicates distance from the epicardial surface to the trough of the intertrabecular recess; and Y, distance from the epicardial surface to the peak of

trabeculation.

Downloaded from http://ahajournals.org by on December 10, 2019

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Introducción: Miocardiopatía no compactada: Diagnóstico.

- Herramienta muy útil para caracterización fenotípica (mayor resolución espacial que ecocardiografía y posibilidad de caracterización miocárdica –RTG).

- Criterios RMC: Petersen, Grothoff, Stacey, Jacquier.

- Criterio Petersen:

Zemrak. JACC 2014 (MESA study). Weir-McCall. JACC 2016 (TASCFORCE study). Petersen. JACC 2005.

- NC/C ratio ≥ 2,3 en telediástole en eje largo.

- ↑ sensibilidad y ↓ especificidad.

- El más empleado en la práctica clínica.

- Utilizando Petersen, hasta el 15% de individuos asintomáticos (sin historia CV) del estudio TASCFORCE y 25% del MESA cumplían criterios de MNC.

RESONANCIA MAGNÉTICA CARDÍACA

(8)

Introducción: Miocardiopatía no compactada: Diagnóstico.

Oechslin. JACC 2018.

dysfunction was a risk factor for MACE in carriers of mutations but not in sporadic cases(9).

LVNC: PHYSIOLOGIC OR PATHOLOGIC REMODELING OF THE MYOCARDIUM?

Noncompaction is the description of a myocardial phenotype with a severely thickened myocardium presenting with a prominent noncompacted layer (excessive trabeculations, deep intertrabecular recesses), which is at least twice as thick as the compacted layer. Different diagnostic criteria are used to diagnose LVNC; although the Jenni criteria are most frequently applied to diagnose LVNC, each of them has its own limitations and pitfalls (15–18).

Recently, clinicians and researchers have debated whether LVNC is a physiologic or a pathologic phenotype of the myocardium. Genetic mutation(s) and nongenetic factors such as loading conditions (volume/pressure load) drive ventricular remodeling (concentric remodeling, concentric/eccentric hypertrophy) and the myocardial phenotype of dilated cardiomyopathy, hypertrophic cardiomyopathy, or LVNC (18–24). Obviously, there seems to be a physiologic, reversible remodeling of the LV myocardium with prominent trabeculations in athletes or pregnant women as opposed to a pathologic ventricular remodeling in patients with a cardiomyopathy of any cause or pathologic remodeling of the myocardium due to pathological loading conditions (Figure 1) (8).

The identification of significantly more frequent genetic mutations in children than in adults, associated with LV systolic dysfunction as a risk factor for MACE, enhances our understanding of LVNC(9). The association between a genetic mutation and LV dysfunction as a risk factor for outcome, with LVNC as the myocardial phenotype, strengthens the hypothesis that LVNC is a genetically determined cardiomyopathy. The results of this study emphasize the importance of routine genetic testing to establish a genotype–phenotype correlation and to move to the next step, from the description of the myocardial phenotype and morphological diagnosis to a genetically confirmed diagnosis. LVNC can occur in isola- tion or in association with other pathologies of the heart (e.g., congenital heart defects), with or without associated gene mutation(s).

We are concerned that a healthy subject not be labeled as a patient with LVNC, with a life-long impact on this individual and on the health care system, with unjustiﬁed regular follow-up visits and tests. This is a call for precaution not to over-diagnose LVNC and to establish the diagnosis of LVNC after a careful comprehensive assessment including genetic testing and concordant morphologic ﬁndings on the echocardiogram and advanced cardiac imaging (e.g., cardiac magnetic resonance).

As volume or pressure load results in hypertrophy of the myocardium, it can also result in the morphological appearance of LVNC, which is different from

F I G U R E 1 Myocardial Phenotype of LVNC to Noncompaction Cardiomyopathy

Non-CompactionLVNC Cardiomyopathy

Pathologic remodelingLVNC (e.g., Pressure / volume load)

Physiologic, reversible remodelingLVNC (e.g., Athletes, pregnancy) Medical history

• Collapse, syncope, arrhythmias, heart failure Electrocardiogram

Cardiac imaging

• Non-compacted layer >> compacted layer; thin compacted layer • LV size / systolic dysfunction

Family history Genetic testing

(Myocardial phenotype)LVNC

From the myocardial phenotype of LVNC to noncompaction cardiomyopathy, pathologic or physiologic reversible remodeling. LVNC ¼ left ventricular noncompaction.

Oechslin and Jenni J A C C V O L . 7 1 , N O . 7 , 2 0 1 8

LV Noncompaction: Remodeling to Cardiomyopathy F E B R U A R Y 2 0 , 2 0 1 8 : 7 2 3 – 6

724

- Algunos autores defienden que la presencia de no compactación

es un epifenómeno de distintas condiciones fisiológicas o

patológicas.

(9)

- En un estudio muy reciente ( UK Biobank ) se ha encontrado una ausencia de asociación entre los extremos de ejercicio físico y el fenotipo de no compactación (con criterio de Petersen).

Introducción: No compactación y ejercicio físico.

Woodbridge. Heart 2019.

- El entrenamiento de alta intensidad se ha asociado con una mayor prevalencia de criterios de MNC utilizando ecocardiografía y RMC.

- Sin embargo, se desconoce si esta asociación también aplica a la población general.

- Objetivo: Evaluar la asociación entre actividad física y fenotipo

de no compactación en población general (cohorte PESA).

(10)

Discusión

• Se ha identificado un patrón ecocardiográfico de no compactación en algunas situaciones de estrés (fisiológico).

478 Circulation August 5, 2014

was determined with the use of the 16-segment model recommended by the American Society of Echocardiography.

¹³

Ethical Approval/Consent

The National Research Ethics Service, East London 2 Research Ethics Committee granted ethical approval in the UK.

Statistical Analysis

Statistical analyses were performed with SPSS version 18.0 (SPSS, Inc, Chicago IL). Variables were tested for normality with the Kolmogorov-Smirnov test. Values are expressed as either mean±SD or percentages as appropriate. Differences within group means were compared by use of the paired Student t test or the Wilcoxon test, and differences between group means were compared by use of inde- pendent t tests or Mann-Whitney U tests (for normally and nonnor- mally distributed variables, respectively). The χ

²

test or Fisher exact test was used as appropriate to test group differences of proportions.

Repeated-measures ANOVA was performed to evaluate changes in the clinical and echocardiographic parameters during pregnancy and the postpartum period. Logistic regression was used to determine multiple-adjusted risk for the presence of increased (≥3) trabecula- tions during pregnancy in relation to ethnicity, age, body mass index, heart rate, blood pressure, LV stroke volume, LV cavity and volume size, and LV mass. Statistical significance was defined as a 2-tailed value of P<0.05 throughout.

Reproducibility of LV and RV measurements was assessed with intraclass correlation coefficient analysis and reported as intraclass correlation coefficient (95% confidence interval). Averaged mea- sures were used as an index for the reliability of 2 different rates.

Intraobserver and interobserver agreement for the presence of LV tra- beculations was assessed by κ statistics.

Results

Subjects

Pregnant women had a mean age of 30.7±4.4 years and a body surface area of 1.8±0.3 m

²

. The majority (64.7%) were white.

None of the women had a family history of cardiomyopathy or premature (<40 years of age) sudden cardiac death. All women were normotensive (blood pressure ≤120/80 mm Hg), and none revealed proteinuria.

Hemodynamic and Structural Changes During Pregnancy

The progression of pregnancy from the first trimester to the third trimester was accompanied by increases in heart rate, stroke volume, and cardiac output and a reduction in total vascular resistance. Advancing pregnancy was also associ- ated with a modest (11%–12%) increase in LV volume and LV mass (Table 1).

Pregnant Women With Increased LV Trabeculations Twenty-five percent of pregnant women developed increased LV trabeculations (Figure 2), which were more common in black women than in white women (47.2% versus 13.6%;

P=0.0003). Of the total pregnancy cohort, 10 women (9.8%) fulfilled the Jenni et al criteria, 19 (18.6%) fulfilled the Chin et al criteria, and 8 (7.8%) fulfilled both criteria for LVNC (Figure 3). Women fulfilling both criteria did not show any significant ethnic predilection (black: n=4, 11.1%; white:

n=4, 6.1%; P=0.459). During pregnancy, the Chin et al X/Y ratio at the site of maximal wall thickness averaged 0.43±0.07 (range, 0.35–0.5), and the Jenni et al ratio of noncompacted to

compacted myocardial at the site of maximal wall thickness averaged 2.2±0.6 (range, 2.1–3.4).

LV trabeculations were distributed predominantly in the anterolateral territory (n=14), followed by the inferolateral (n=7), inferior (n=7), apical lateral (n=7), and apical inferior (n=6) regions.

Differences in ECG and Echocardiographic Parameters in Pregnant Women Exhibiting Increased LV Trabeculations and Those With Normal Cardiac Morphology

Pregnant women who developed LV trabeculations did not differ from those without LV trabeculations in terms of elec- trocardiographic abnormalities. One pregnant woman with LV trabeculations showed minor T-wave inversion in leads V

₁

and V

₂

on the baseline ECG, as did 1 woman with normal myo- cardial morphology, which persisted during pregnancy and for 12 months postpartum. There were no significant differences in wall thickness, cavity size, indexes of systolic and diastolic function, or stroke volume between the women in the 2 groups (Table 2). None of the women in the study exhibited abnormal systolic or diastolic function.

Figure 2. A 2-dimensional echocardiographic example of a woman who developed de novo left ventricular (LV) trabeculations during the progression of pregnancy, which regressed in the postpartum period.

Figure 3. A 2-dimensional echocardiographic example of 1 of 8 women who fulfilled both the Chin et al² criteria and Jenni et al³ criteria for noncompaction during the third trimester of pregnancy. C indicates compacted layer; NC, noncompacted layer; X, distance from the epicardial surface to the trough of the intertrabecular recess; and Y, distance from the epicardial surface to the peak of trabeculations.

475

L

eft ventricular (LV) noncompaction (LVNC) cardiomyopathy is an unclassified primary cardiomyopathy characterized by increased myocardial trabeculations and recesses. The precise stage of development and the natural history of the con- dition are not fully understood; however, preliminary data are indicative of a morphologically and clinically heterogeneous disorder. Some individuals present with overt heart failure, fatal arrhythmias, and thromboembolic events, and others remain asymptomatic.¹ Echocardiographic criteria to facilitate the identification and assessment of LVNC rely on the presence of LV myocardial trabeculations and a 2-layer distinction between compacted and noncompacted myocardium (Figure 1).^2–5

Editorial see p 453 Clinical Perspective on p 483

The past 2 decades have witnessed significant advances in tissue harmonics, which have enabled detailed assessment of the ventricular myocardium. Such progress in image resolution has coincided with an increasing number of scientific reports relating to LVNC. The initial prevalence of LVNC was estimated to be <0.3%.^2,6 However, recent studies in patients with heart failure have reported a high proportion (almost 35%) of patients with myocardial trabeculations, with nearly 25% fulfilling diagnostic criteria for LVNC regardless of the criteria used.⁷ A study of >1000 athletes demonstrated that 18% exhibited increased LV trabeculations and 8% fulfilled echocardiographic criteria for LVNC.⁸ Patients with sickle cell anemia also reveal a high (28.3%) prevalence of increased LV trabeculations.⁹ A common theme among all 3 cohorts is the presence of an increased cardiac preload. Given the relatively Background—Patients with heart failure and chronic anemia frequently demonstrate left ventricular (LV) trabeculations, which may be compatible with the diagnosis of LV noncompaction. We used the pregnancy model, which is characterized by a reversible increase in cardiac preload and other changes in cardiac function, to assess the development of de novo LV trabeculations in women with morphologically normal hearts.

Methods and Results—One hundred two primigravida pregnant women were evaluated longitudinally with a series of echocardiograms in the first trimester, in the third trimester, and postpartum. Echocardiograms were analyzed according to established guidelines. Increased LV trabeculations and the presence of LV noncompaction were based on established criteria. Pregnancy was associated with an increased heart rate, stroke volume, and cardiac output, as well as increased LV volume and mass. During pregnancy, 26 women (25.4%) developed increased trabeculations. Eight women showed sufficient trabeculations to fulfill criteria for LV noncompaction. During the postpartum follow-up period of 24±3 months, 19 women (73%) demonstrated complete resolution of trabeculations, and 5 showed a marked reduction in the trabeculated layer.

Conclusions—Pregnancy induces de novo LV trabeculations in a significant proportion of women. The results suggest that LV trabeculations occur in response to increased LV loading conditions or other physiological responses to pregnancy and are not specific for LV noncompaction. These factors should be considered in the assessment of individuals with LV trabeculations outside the context of symptoms of heart failure or familial cardiomyopathy. (Circulation.

2014;130:475-483.)

Key Words: cardiomyopathies ◼ echocardiography ◼ ethnic groups ◼ isolated noncompaction of the ventricular myocardium ◼ pregnancy

Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.114.008554

Received January 8, 2014; accepted May 30, 2014.

From St. George’s University of London, London, UK (S.G., M.P., A.Z., N.S., M.R., R.S., B.T., S.S.); and University Hospital Lewisham, London, UK (S.G., N.D.P.).

Correspondence to Sanjay Sharma, BSc (Hons), MD, FRCP, FESC, Professor of Clinical Cardiology, St. George’s University of London, Cranmer Terrace, London SW17 0RE, UK. E-mail [email protected]

Reversible De Novo Left Ventricular Trabeculations in Pregnant Women

Implications for the Diagnosis of Left Ventricular Noncompaction in Low-Risk Populations

Sabiha Gati, BSc (Hons), MRCP; Michael Papadakis, MRCP, MD;

Nikolaos D. Papamichael, MD; Abbas Zaidi, MRCP, MD;

Nabeel Sheikh, BSc (Hons), MRCP; Matthew Reed, BSc; Rajan Sharma, MD, FRCP;

Baskaran Thilaganathan, BSc (Hons), PhD, FRCOG; Sanjay Sharma, BSc (Hons), MD, FRCP, FESC

Imaging

Gati. Circulation 2014.

- 102 embarazadas evaluadas longitudinalmente con ecocardiografía.

- Una cuarta parte de ellas (25,4%)

desarrollaron hipertrabeculación

durante el embarazo, que se resolvió en

el postparto.

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Discusión

• “Un ventrículo trabeculado vs. no trabeculado puede trabajar con menor strain para generar el mismo volumen latido.

Bruno. Int J for numerical methods in biomedical engineering 2018.

Relationship between the left ventricular size and the amount of trabeculations

Bruno Paun, Bart Bijnens, Constantine Butakoff*

Using a geometrical model of the left ventricle we show that: a trabeculated ventricle can work at lower strains compared to a nontrabeculated one to produce the same stroke volume;

the trabeculations can help increasing stroke volume with less strain; it is possible to find an optimal amount of trabeculations, where SV is optimized while LV size remains within physiological ranges; the trabeculations are necessary for a more efficient cardiac function, even a small amount of them can be beneficial.

• Las trabéculas podrían ser un mecanismo

compensatorio en algunas situaciones fisiológicas

(embarazo, ejercicio

físico…) para generar

un gasto cardiaco

extra sin aumentar el

estrés del VI.

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Conclusión

• Los criterios actuales de imagen (RMC) son excesivamente sensibles para detección de MNC .

Pelliccia. EHJ 2018.

.. ..

supportive features include LV systolic dysfunction, with reduced

.

(<50%) ejection fraction, but also a very thin compacted epicardial layer (i.e. <8 mm in systole on echocardiography)⁶⁴ and abnormal myocardial relaxation (e⁰<9 cm/s at TDI.⁶⁵

Athletes frequently show increased trabeculations in the LV cavity (i.e. so-called hypertrabeculation pattern), and up to 8% may fulfil the morphological criteria for LVNC.⁶⁵ It has been postulated that an increased cardiac preload may simply unmask pre-existing trabeculations and make them more prominent. This hypothesis is supported by a longitudinal study, using the pregnancy model, which showed that almost 25% of primigravida women developed prominent trabeculation and 8% fulfilled criteria consistent with LVNC as pregnancy progressed to the third trimester.⁶⁶

Only a small proportion (0.9%) of athletes with hypertrabeculation exhibit other clinical abnormalities supportive for diagnosis of a cardiomyopathy; these athletes need to be thoroughly inves- tigated.⁶⁵ Specifically, athletes with LV hypertrabeculation and an abnormal ECG and/or mildly reduced LV function, or positive family history should undergo a complete evaluation including CMR and exercise echocardiography to assess the LV response to effort, and ECG Holter monitoring to ascertain the presence of arrhythmias, all findings that will support the diagnosis of LVNC.^6,65,66–70

Risk stratification

The clinical outcome of LVNC is variable, even within families, and governed by the magnitude of LV dysfunction and prevalence of atrial and ventricular arrhythmias or thromboembolic events. Adverse consequences are largely associated with LV systolic dysfunction or major ventricular tachyarrhythmias. It is noteworthy that no major cardiac events have been reported in the absence of LV dysfunction, regardless the severity of hypertrabeculation.^65,67–70

Recommendations

As specified above, advising an individual with LVNC regarding participation to competitive sport requires a comprehensive and clear explanation, and assurance of understanding of the associated risks on behalf of the candidate (Table5).

Arrhythmogenic (right

ventricular) cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC), or simply arrhythmogenic cardiomyopathy (AC) is an inherited myocardial disease caused predominantly by mutations in genes encoding desmo- somal proteins. The disease is characterized histologically by fibro- fatty replacement of the right ventricle and/or LV myocardium, and clinically by life-threatening ventricular tachyarrhythmias.⁷¹ Sudden death usually occurs in young AC individuals and is often triggered by exercise. Arrhythmogenic cardiomyopathy represents a common cause of SCD in prospective studies of young athletes in Italy⁷²and in an unselected population of young adults from Australia.⁷³

The diagnosis of AC is based on the criteria proposed by an expert consensus panel that recognize electrophysiological, anatomical, and clinical features of the disease.⁷⁴

12-lead ECG

The ECG is of particular value in raising suspicion for AC and is abnormal in the majority (>60%) of individuals.⁷⁵The most common abnormalities in the right-dominant variant include inverted T-waves in the right precordial leads (V1–V3), prolonged QRS duration >110 ms with right bundle branch block (RBBB) pattern and a delayed upstroke (>55 ms) of the S wave in V1–V2. Rare is the presence of an epsilon wave in V1 or V2. In the left-dominant variant low voltages of R/S wave in the limb leads are increasingly recognized, as well as the presence of diffuse

...

Table 5 Recommendations for athletes with LVNC

Class/level of evidence 1. Athletes with incidental discovery of LV hypertrabeculation should not be diagnosed as LVNC in the absence of

symptoms, positive family history, abnormal ECG patterns and, most importantly, impaired LV function. In such cases, no restriction for all competitive sports apply.

Class IIa/Level B

2. Athletes with unequivocal/reasonable diagnosis of LVNC but near-normal LV systolic function may participate in all competitive sports, with the exception of those where occurrence of syncope may cause serious harm or death (Figure1), if they are:

(1) asymptomatic,

(2) without frequent and/or complex ventricular arrhythmias, or non-sustained VT on ambulatory monitoring and exercise ECG testing, and

(3) no prior history of unexplained syncope

Class IIb/ Level C

3. Athletes with an unequivocal diagnosis of LVNC and (1) impaired LV systolic function and/or

(2) frequent and/or complex ventricular arrhythmias, or non-sustained VT on ambulatory monitoring or exercise testing should be advised to abstain from participation in competitive sports.

Class III/ Level C

These patients should be advised to limit their exercise programmes to leisure-time physical activities and remain under regular clinical surveillance.

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